This proposal aims to apply the most modern techniques in biomechanics and biochemistry to survey the variations in composition, molecular structure of collagen and proteoglycans, and mechanical properties of normal young, aging, and osteoarthritic human articular cartilage. The study will focus on the biochemical role of the collagen network structure in controlling the strength and stiffness of articular cartilage as manifested by the specimens' tensile and swelling behavior, and the role of proteoglycan aggregation, molecular size, and polydispersity in controlling cartilage compressive stiffness, permeability to fluid flow and swelling. Particular emphasis will be given to identifying those changes in composition, molecular architecture, and mechanical properties of cartilage which occur as a result of the normal aging process and osteoarthritic degeneration, and the correlations which might exist among the measured parameters. Emphasis is also placed in identifying functional reasons for the natural variations in properties over the joint surface and through the cartilage thickness. The long-term objective of this work is to forge a close, collaborative relationship between the diverse disciplines of biomechanics and biochemistry by focusing on the problem of understanding articular cartilage degeneration in aging and osteoarthritis. The basic understanding achieved here is a necessary prelude toward the development of rational therapeutic measures for the treatment of osteoarthritic degeneration.